Polymorphisms in GSDMA and GSDMB are Associated With Asthma Susceptibility, Atopy and BHR

被引：85

作者：

Yu, Jinho ^{[2
]}

Kang, Mi-Jin ^{[3
]}

Kim, Byoung-Ju ^{[4
]}

Kwon, Ji-Won ^{[2
]}

Song, Young-Hwa ^{[2
]}

Choi, Won-Ah ^{[3
]}

Shin, Yee-Jin ^{[1
]}

Hong, Soo-Jong ^{[2
]}

机构：

[1] Yonsei Univ, Coll Med, Dept Psychiat, Seoul 120752, South Korea

[2] Univ Ulsan, Coll Med, Dept Pediat, Seoul, South Korea

[3] Univ Ulsan, Asan Inst Life Sci, Seoul, South Korea

[4] Inje Univ, Haeundae Paik Hosp, Dept Pediat, Gimhae, South Korea

来源：

PEDIATRIC PULMONOLOGY | 2011年 / 46卷 / 07期

关键词：

asthma; bronchial hyperresponsiveness; GSDMA; GSDMB; IgE; ORMDL3; EXPRESSION; GENE; VARIANTS; FAMILY; 17Q21; GASDERMIN; CHILDREN; ONSET;

D O I：

10.1002/ppul.21424

中图分类号：

R72 [儿科学];

学科分类号：

100202 ;

摘要：

The gasdermin A (GSDMA) and gasdermin B (GSDMB) genes are located at 17q21.2. The GSDM family genes have been studied in the gastrointestinal tract but recent reports suggest that GSDMB is associated with childhood asthma in several populations. We investigated the association of the GSDMA and GSDMB variants with asthma in Korean children, and to assess the effect of these variants on intermediate phenotypes of asthma. Asthmatic (n = 778) and normal (n = 522) children were enrolled and genotypes were determined using PCR-RFLP. Asthma susceptibility was associated with GG of the GSDMA (rs7212938) and TT of GSDMB (rs7216389). And a combination of risk alleles of two polymorphisms was associated with asthma susceptibility and a frequency of those was higher in asthmatic children with increased levels of total IgE (aOR 1.77, 95% CI 1.15-2.72) and BHR (aOR 1.54, 95% CI 0.99-2.40) compared to normal. Also, we observed a significant association between haplotype of two polymorphisms and asthma susceptibility. The region including the GSDMA and GSDMB polymorphisms may be associated with asthma susceptibility and intermediate phenotypes of asthma, such as elevated IgE and BHR, in Korean children with asthma. These results strongly support an important role for the GSDMA and GSDMB in the development of childhood asthma. Pediatr Pulmonol. 2011;46:701-708. (C) 2011 Wiley-Liss, Inc.

引用

页码：701 / 708

页数：8

共 22 条

[1] Effect of 17q21 Variants and Smoking Exposure in Early-Onset Asthma [J].

Bouzigon, Emmanuelle ;

Corda, Eve ;

Aschard, Hugues ;

Dizier, Marie-Helene ;

Boland, Anne ;

Bousquet, Jean ;

Chateigner, Nicolas ;

Gormand, Frederic ;

Just, Jocelyne ;

Le Moual, Nicole ;

Scheinmann, Pierre ;

Siroux, Valerie ;

Vervloet, Daniel ;

Zelenika, Diana ;

Pin, Isabelle ;

Kauffmann, Francine ;

Lathrop, Mark ;

Demenais, Florence .

NEW ENGLAND JOURNAL OF MEDICINE, 2008, 359 (19) :1985-1994

[2] Orm family proteins mediate sphingolipid homeostasis [J].

Breslow, David K. ;

Collins, Sean R. ;

Bodenmiller, Bernd ;

Aebersold, Ruedi ;

Simons, Kai ;

Shevchenko, Andrej ;

Ejsing, Christer S. ;

Weissman, Jonathan S. .

NATURE, 2010, 463 (7284) :1048-U65

[3] The asthma-associated ORMDL3 gene product regulates endoplasmic reticulum-mediated calcium signaling and cellular stress [J].

Cantero-Recasens, Gerard ;

Fandos, Cesar ;

Rubio-Moscardo, Fanny ;

Valverde, Miguel A. ;

Vicente, Ruben .

HUMAN MOLECULAR GENETICS, 2010, 19 (01) :111-121

[4] STANDARDIZATION OF BRONCHIAL INHALATION CHALLENGE PROCEDURES [J].

CHAI, H ;

FARR, RS ;

FROEHLICH, LA ;

MATHISON, DA ;

MCLEAN, JA ;

ROSENTHAL, RR ;

SHEFFER, AL ;

SPECTOR, SL ;

TOWNLEY, RG .

JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, 1975, 56 (04) :323-327

[5] The immunogenetics of asthma and eczema: A new focus on the epithelium [J].

Cookson, W .

NATURE REVIEWS IMMUNOLOGY, 2004, 4 (12) :978-988

[6] ORMDL3 gene is associated with asthma in three ethnically diverse populations [J].

Galanter, Joshua ;

Choudhry, Shweta ;

Eng, Celeste ;

Nazario, Sylvette ;

Rodriguez-Santana, Jose R. ;

Casal, Jesus ;

Torres-Palacios, Alfonso ;

Salas, Jorge ;

Chapela, Rocio ;

Watson, H. Geoffrey ;

Meade, Kelley ;

LeNoir, Michael ;

Rodriguez-Cintron, William ;

Avila, Pedro C. ;

Burchard, Esteban Gonzalez .

AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, 2008, 177 (11) :1194-1200

[7] A sequence variant on 17q21 is associated with age at onset and severity of asthma [J].

Halapi, Eva ;

Gudbjartsson, Daniel F. ;

Jonsdottir, Gudrun M. ;

Bjornsdottir, Unnur S. ;

Thorleifsson, Gudmar ;

Helgadottir, Hafdis ;

Williams, Carolyn ;

Koppelman, Gerard H. ;

Heinzmann, Andrea ;

Boezen, H. Marike ;

Jonasdottir, Aslaug ;

Blondal, Thorarinn ;

Gudjonsson, Sigurjon A. ;

Jonasdottir, Adalbjorg ;

Thorlacius, Theodora ;

Henry, Amanda P. ;

Altmueller, Janine ;

Krueger, Marcus ;

Shin, Hyoung Doo ;

Uh, Soo-Taek ;

Cheong, Hyun Sub ;

Jonsdottir, Brynja ;

Ludviksson, Bjorn R. ;

Ludviksdottir, Dora ;

Gislason, David ;

Park, Choon-Sik ;

Deichmann, Klaus ;

Thompson, Philip J. ;

Wjst, Matthias ;

Hall, Ian P. ;

Postma, Dirkje S. ;

Gislason, Thorarinn ;

Kong, Augustine ;

Jonsdottir, Ingileif ;

Thorsteinsdottir, Unnur ;

Stefansson, Kari .

EUROPEAN JOURNAL OF HUMAN GENETICS, 2010, 18 (08) :902-908

[8] Genetic polymorphism regulating ORM1-like 3 (Saccharomyces cerevisiae) expression is associated with childhood atopic asthma in a Japanese population [J].

Hirota, Tomomitsu ;

Harada, Michishige ;

Sakashita, Masafumi ;

Doi, Satoru ;

Miyatake, Akihiko ;

Fujita, Kimie ;

Enomoto, Tadao ;

Ebisawa, Motohiro ;

Yoshihara, Shigemi ;

Noguchi, Emiko ;

Saito, Hirohisa ;

Nakamura, Yusuke ;

Tamari, Mayumi .

JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, 2008, 121 (03) :769-770

[9] Gene-gene interaction between interleukin-4 and interleukin-4 receptor α in Korean children with asthma [J].

Lee, SG ;

Kim, BS ;

Kim, JH ;

Lee, SY ;

Choi, SO ;

Shim, JY ;

Hong, TJ ;

Hong, SJ .

CLINICAL AND EXPERIMENTAL ALLERGY, 2004, 34 (08) :1202-1208

[10] Asthma and atopy are associated with chromosome 17q21 markers in Chinese children [J].

Leung, T. F. ;

Sy, H. Y. ;

Ng, M. C. Y. ;

Chan, I. H. S. ;

Wong, G. W. K. ;

Tang, N. L. S. ;

Waye, M. M. Y. ;

Lam, C. W. K. .

ALLERGY, 2009, 64 (04) :621-628

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